Tessier Laurence, Gagnon Ann-Lorie, St-Amour Sophie, Côté Mathilde, Allard Catherine, Durand Mathieu, Bergeron Danny, Lavoie Alexandre, Michaud-Herbst Alban, Tremblay Karine
Pharmacology-Physiology Department, Université de Sherbrooke, Saguenay, QC, Canada.
Centre de recherche et d'innovation du Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean (CIUSSS-SLSJ), 225, St-Vallier Street Pavillon des Augustines, Saguenay, QC, G7H 7P2, Canada.
Sci Rep. 2025 May 25;15(1):18240. doi: 10.1038/s41598-025-02463-4.
For severe forms of ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), biological therapies, including tumor necrosis factor inhibitors (anti-TNF), are often used. However, these drugs have a high variability in treatment response. Multiple factors, such as genetic variants, can affect this variability. The goal of the study was to verify if selected candidate variants could affect response to anti-TNF in UC treatment. This association study included 76 participants suffering from UC and past or current users of anti-TNF. Clinical data for phenotyping was collected through a single visit with the participant and a medical chart review. Blood or saliva samples were collected to extract DNA and to genotype eight selected candidate variants in genes TNF, TNFAIP3, TNFRSF1 A and TNFRSF1B. For anti-TNF users, 30% of individuals were non-responders, 70% suffered from AE and none of the studied variants was associated with the response's phenotype. However, for infliximab users only (n = 44), the TNFRSF1B-rs1061622 variant was associated with nonresponse to infliximab for the first time in a cohort of UC patients (p-value = 0.028). Next steps are to replicate this association in independent cohorts and to perform functional studies to gain more evidence on the variant.
对于重度溃疡性结肠炎（UC）这种慢性炎症性肠病（IBD），通常会使用包括肿瘤坏死因子抑制剂（抗TNF）在内的生物疗法。然而，这些药物的治疗反应存在很大差异。多种因素，如基因变异，可影响这种差异。该研究的目的是验证选定的候选变异是否会影响UC治疗中对抗TNF的反应。这项关联研究纳入了76名患有UC且曾使用或正在使用抗TNF的参与者。通过与参与者的单次访视和病历审查收集用于表型分析的临床数据。采集血液或唾液样本以提取DNA，并对TNF、TNFAIP3、TNFRSF1A和TNFRSF1B基因中的八个选定候选变异进行基因分型。对于抗TNF使用者，30%的个体无反应，70%的个体出现不良事件，且所研究的变异均与反应表型无关。然而，仅对于英夫利昔单抗使用者（n = 44），TNFRSF1B-rs1061622变异在一组UC患者中首次与对英夫利昔单抗无反应相关（p值 = 0.028）。接下来的步骤是在独立队列中重复这种关联，并进行功能研究以获取更多关于该变异的证据。
